Thromboxane (TX) B₂, the chemically stable hydration product of pro-aggregatory TXA₂, undergoes two major pathways of metabolism in man, resulting in the formation of 2,3-dinor-TXB₂ and 11-dehydro-TXB₂, respectively. We have measured the excretion of the latter during the infusion of exogenous TXB₂ over a 50-fold dose range in order to examine the fractional conversion of TXB₂ to urinary 11-dehydro-TXB₂ and to re-assess the rate of entry of endogenous TXB₂ into the circulation. Four healthy male volunteers receeived 6-h intravenous infusions of the vehicle alone and TXB₂ at 0.1, 1.0 and 5.0 ng · kg⁻¹ · min⁻¹ in random order. They were pretreated with aspirin 325 mg/d in order to suppress endogenous TXB₂ production. Urinary 11-dehydro-TXB₂ and 2,3-dinor-TXB₂ were measured before, during and up to 24 h after the infusions and in aspirin-free periods, by means of NICI-GC/MS-validated radioimmunoassays. Aspirin treatment suppressed urinary 11-dehydro-TXB₂ by 91%. The fractional elimination of 11-dehydro-TXB₂ was independent of the rate of TXB₂ infusion and averaged 6.8 ± 0.7%, as compared to 6.4 ± 0.9% for 2,3-dinor-TXB₂. Interpolation of 11-dehydro-TXB₂ values obtained in aspirin-free periods onto the linear relationship between the quantities of infused TXB₂ and the amount of metabolite excreted in excess of control values (y = 0.0058x, r = 0.94, P < 0.001) permitted calculation of the mean rate of entry of endogenous TXB₂ into the circulation as 0.12 ng · kg⁻¹ · min⁻¹. We conclude that: (a) urinary 11-dehydro-TXB₂ is at least as abundant a conversion product of exogenously infused TXB₂ as 2,3-dinor-TXB₂; (b) its excretion increases linearly as a function of the rate of entry of TXB₂ into the circulation up to approx. 40-fold the calculated rate of secretion of endogenous TXB₂; (c) the latter is consistent with previous estimates based on monitoring of the β-oxidation pathway of TXB₂ metabolism.